Alkynes are very important building blocks in synthetic chemistry and in material science and they are also a common motif in pharmaceuticals. The unique physical properties of alkynes (rigid structure and conjugating π system) make them an attractive functional group for unsaturated molecular scaffolds. Because of their unsaturated, high-energy structure further derivatization in many synthetic transformations (including cycloaddition, metathesis, click reaction etc.) may be possible and leads to various useful molecules.
The development of catalytic system for direct conversion of inert C—H bonds into C-alkynyl bonds is very attractive, simplest and sustainable method as the alkyne moiety is of significant importance for various organic transformations including cycloaddition, metathesis, click reaction etc. In addition alkynes are outstanding building blocks in synthetic chemistry and in material science and they are also a common motif in drugs. Because of the susceptibility of terminal alkynes to homocoupling under the commonly employed oxidative reaction conditions, C—H alkynylation is largely underexplored.
Catalysts based direct activation of C—H bonds provides a sustainable and an atom-economical synthetic strategy to diverse organic molecules from simple, pre-functionalized substrates. The selection of ligands is very crucial in the design of such active catalytic systems. Ligands would alter the electronic and steric properties of the active catalyst and thus they could significantly accelerate C—H activation and successive bond forming reactions. Although, ligand-enabled C(sp3)-H activation has emerged as a powerful tool for rapid, straightforward construction of the carbon-carbon and the carbon-heteroatom bonds, there still remains a significant challenge in the field of C(sp3)-H activation.
Article titled “Rhodium(III)-catalyzed alkenylation reactions of 8-methylquinolines with alkynes by C(sp3)-H activation” by B Liu et al. published in Angew Chem. Int Ed Engl., 2014; 53(16), pp 4191-4195 reports alkenylation reactions of 8-methylquinolines with alkynes, catalyzed by [{Cp*RhCl2}2], proceeds efficiently to give 8-allylquinolines in good yields by C(sp3)-H bond activation. These reactions are highly regio- and stereoselective.

Article titled “Palladium-Catalyzed Direct Ethynylation of C(sp3)-H Bonds in Aliphatic Carboxylic Acid Derivatives” by Y Ano et al. published in J. Am. Chem. Soc., 2011, 133 (33), pp 12984-12986 reports first catalytic alkynylation of unactivated C(sp3)-H bonds by straightforward introduction of an ethynyl group into aliphatic acid derivatives under palladium catalysis. This new reaction can be applied to the rapid elaboration of complex aliphatic acids, for example, via azide/alkyne cycloaddition.

Article titled “Palladium(0)-Catalyzed Alkynylation of C(sp3)-H Bonds” by J He et al. published in J. Am. Chem. Soc., 2013, 135 (9), pp 3387-3390 reports alkynylation of β-C(sp3)-H bonds in aliphatic amides with alkynyl halides enabled using Pd(0)/N-heterocyclic carbene (NHC) and Pd(0)/phosphine (PR3) catalysts.
Article titled “Direct palladium-catalyzed C-3 alkynylation of indoles” by Y Gu et al. published in Tetrahedron Letters, 2009, 50 (7), pp 763-766 reports direct palladium-catalyzed coupling reaction of indoles with alkynyl bromides In the presence of catalytic amount of PdCl2(PPh3)2 and 2.0 equiv. NaOAc, the coupling reaction of indoles with alkynyl bromides proceeded smoothly at 50° C. to give the corresponding 3-alkynylindoles with high regioselectivity in good to excellent yields.

Article titled “Direct Palladium-Catalyzed Alkynylation of N-Fused Heterocycles” by N Seregin et al. published in J. Am. Chem. Soc., 2007, 129 (25), pp 7742-7743 reports direct C—H alkynylation of electron-rich heteroaromatics. This mild, simple, and general method allows for the efficient synthesis of diverse alkynyl heterocycles.

Article titled “Catalytic Coupling of C—H and C—I Bonds Using Pyridine As a Directing Group” by D Shabashov et al. published in Org. Lett., 2005, 7 (17), pp 3657-3659 reports a method for the palladium-catalyzed arylation of pyridines and pyrazoles. Both aliphatic and aromatic C—H bonds may be functionalized using this method. A bromo substituent is tolerated on the aryl iodide coupling component.
The prior art reports C—H alkynylation of aliphatic carboxylic acid derivatives using template strategy. Due to cyclometalation ability of 8-methylquinoline several transition-metal-catalyzed C(sp3)-H bond activation of 8-methylquinoline has been reported by various research groups. Despite a number of reports concerning C(sp2)-H alkynylation reactions, methods to convert C(sp3)-H bonds to C(sp3)-alkynyl bonds remain extremely rare. Accordingly, the present invention provides efficient C—H alkynylation of inert C(sp3)-H bonds of N-heterocycles.
The main objective of the present invention is to provide N-heterocyclic compounds of formula A.
Another objective of the present invention is to provide a process for the preparation of N-heterocyclic compounds of formula A.
Yet another objective of the present invention is to provide N-heterocyclic compounds of formula A useful for ligand synthesis in transition-metal catalysis.
Yet another objective of the present invention is to provide a ligand-enabled palladium-catalyzed straightforward and efficient C—H alkynylation of inert C(sp3)-H bonds of N-heterocycles (quinoline and pyridine derivatives) using a chelation-assisted strategy.